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Objectives: Circular RNAs (circRNAs), with their multilevel and versatile regulation, have emerged as promising targets for treating complex and heterogeneous malignancies such as oral squamous cell carcinoma (OSCC). It is crucial to explore the function of key circRNAs and elucidate the underlying mechanisms to establish an effective in vivo delivery system to better utilize circRNAs as cancer treatment strategies. Materials and Methods: circRNA (circ‐OCAC) was identified as significantly downregulated in tumor samples compared to paracancerous tissues by RNA‐seq analysis of eight pairs of OSCC tissues. Functional experiments of circ‐OCAC were performed both in vitro and in vivo. The interactions between circ‐OCAC and miR‐411‐5p were clarified by RNA pull down and RNA immunoprecipitation (RIP) assays. Results: We observed that circ‐OCAC inhibits OSCC growth and metastasis by blocking the PI3K/Akt signaling pathway. To translate this observation in vivo, a pH‐responsive nanoparticle (pNP) was developed to target circ‐OCAC. Our results confirmed the advantages of the pNP‐circ‐OCAC system: high tumor enrichment capacity and good biosafety, which resulted in a significantly enhanced antitumor effect. Conclusions: This study demonstrated that targeting circ‐OCAC serves as a promising potential therapeutic strategy for OSCC. [ABSTRACT FROM AUTHOR]